Neuromodulation: advances in the next five years

Neuromodulation (deep brain stimulation; DBS) has become an established treatment for movement disorders (e.g., Parkinson's disease), and is in trials for refractory epilepsy, headache, and certain mood disorders. Two main themes will advance DBS significantly in the next five years: closed-loop DBS, that is, feedback from brain electrical activity to direct the stimulation; and computational analysis (CA)--electrophysiological modeling to enhance DBS. Closed-loop DBS is currently in clinical trials for refractory epilepsy. New imaging techniques offer preoperative modeling for DBS surgery, including nerve fiber tracts (diffusion tensor imaging), and imaging of volume of tissue activated by a specific electrode. CA techniques for DBS include mathematical models of the abnormally synchronized electrical activity which underlies epilepsy, movement disorders, and likely many mood disorders as well. By incorporating feedback loops and multiple recording and/or stimulating sites, the abnormally synchronized brain electrical activity can be desynchronized, then "unlearned" ("unkindling" in epilepsy). Characteristics of DBS utilizing CA include low frequency rather than high frequency stimulation; multiple stimulation and/or recording sites; likely 10-fold or more reduction in electrical current needs (much smaller "pulse generators"); more focused and less disruptive stimulation--fewer unwanted side effects; and potential to "cure" certain disorders by resetting abnormal firing patterns back to normal. These advantages of more sophisticated DBS techniques bring the following challenges, which may require a decade of research before reaching clinical practice because many brain disorders involve neurotransmitter abnormalities (e.g., dopamine in Parkinson's disease and certain mood disorders). Namely, how do we monitor and modulate neurotransmitters in addition to electrical activity? How do we get multiple microelectrodes into the brain in a minimally invasive manner? In the accompanying article, I address these two issues and offer some potential solutions.